Five Important Themes to Watch in the Reform of FDA’s Off-Label Communications Policy

As we’ve previously reported, FDA has recently been forced to reexamine its legal position and enforcement policies related to drug and device manufacturers’ off-label communications. Although the Agency has for years resisted calls to loosen its long-standing prohibitions on the off-label promotion of unapproved products, it has simultaneously recognized that truthful and non-misleading scientific or medical information coming from manufacturers about their own drug, biologic, and device products plays an important role in the U.S. health care system. This has especially been true in a climate where individual products are becoming more complex; precision medicine approaches to treating disease are gaining ground in clinical practice; and the health system is evolving into one more focused on outcomes and value-based arrangements between entities. The expansion of First Amendment commercial speech principles by the courts over the past decade and lawsuits against FDA also have pushed the Agency to move towards the potential reform of its existing off-label policies.

FDA recently held a highly anticipated public hearing to allow different stakeholders to express their distinct viewpoints regarding the appropriate regulatory approach to manufacturers’ communications about off-label uses for their marketed products. Over the course of those two days, the panel of FDA officials convened for the event (as well as those of us in attendance or watching via webcast) heard perspectives from representatives of drug and device manufacturers, health care professionals, patients and caregivers, patient advocacy groups, research institutions, insurers and other payors. Although the presentations and discussions raised many more questions than it provided answers, we took away 5 recurring themes from this hearing on off-label communications.

Our “Top 5 Themes” of the Off-Label Hearing

Different Rules Are Needed for Different Circumstances. Companies and trade groups argued that FDA cannot maintain a “one-size-fits-all” policy for two main reasons – not all communications are created equal, and not all products have the same risks associated with off-label use. For example, medical device manufacturers advocated for their own policy approach in light of the training and ongoing technical support they provide to users of complex medical devices. Stakeholders asked the Agency to delineate the permissible scope of each particular type of communication and to define those “safe harbors” clearly and with sufficient detail to eliminate the uncertainty that currently abounds when it comes to certain types of truthful and non-misleading scientific exchange. Allowing manufacturers to engage in narrowly defined communications that are put into proper context with appropriate disclaimers, certifications, or other protections in place (like the current framework for providing off-label reprints to health care professionals) seemed to have numerous supporters. Other suggested approaches included the development of an adverse event reporting system for off-label uses only.

Off-Label Information Should Be Shared with Health Plans and Payors. Manufacturer entities, as well as health plans and payors who also addressed the panel, urged FDA to create a safe harbor that would permit product developers to share information with payors about their products before approval, while a new or supplemental application is undergoing FDA review. Harms to patients can accrue when an insurer does not have enough clinical data to make a coverage decision about a medically accepted off-label use for a product, because often the product manufacturer is the best source of such clinical information given its comprehensive monitoring of its product’s risks and benefits. Representatives of both manufacturers and health plans pointed out that health plans and payors are extremely sophisticated recipients of data and information, and as such would be appropriate recipients of off-label information.

Lack of Drug Development Specific to Vulnerable Populations Encourages Off-Label Uses, and Increased Communication Would Protect Those Patients. Many off-label uses for approved products are a consequence of the lack of drugs developed specifically for pediatric populations or for certain rare disease indications. A patient advocacy group explained that pediatric cancer patients routinely receive off-label treatments with drugs, biologics, and medical devices because no cancer treatment is specifically approved by FDA for pediatric use. And physicians pointed out that many drugs are useful in treating ophthalmological diseases and conditions, even though FDA has not approved such indications, and cutting off the flow of scientific data to treating physicians will restrict the ability of doctors to provide effective treatments. Clinicians and other practitioners treating these uniquely vulnerable populations desire easy access to relevant, legitimate data about risks and alternative dosing regimens, which, again, product manufacturers may be in the best position to provide. However, the participants making this argument agreed that manufacturers must be required to provide some certification or statement about the degree of reliability of such data.

Adverse Events Associated with Off-Label Uses May Be Tempered with More Off-Label Communications. As FDA Commissioner Califf noted in his remarks at the start of the hearing, off-label uses are typically associated with more adverse events than approved uses for the same drug. Patients as well as some patient advocacy groups strongly opposed any loosening of off-label communication rules, in part due to these increased safety risks and specific examples of serious patient harms or death as a consequence of an unapproved use. Other patient advocacy groups, however, argued that off-label communications should be permitted to expand legitimate treatment options but with certain patient protections, such as informed consent from the patient and the existence of sufficient literature supporting the off-label treatment’s safety and effectiveness. The unanswerable question underpinning these arguments is: Would there be fewer, or less serious, adverse experiences associated with off-label use if clinicians were better informed about the parameters of an off-label use.

Off-Label Communications Are Valuable in Precision Medicine. The advancement and success of precision medicine – where knowledge of disease subtypes and a patient’s specific genetic and metabolic profile is used to tailor treatment towards the best possible outcome – could be directly impacted by manufacturers’ ability to share information with other health care stakeholders. Developers of genetic tests and screening devices explained that new evidence and uses for those tests are constantly being published in the medical literature and such evidence should be available to guide clinicians when they are making treatment or dosing decisions for patients.

Persons who may want to watch the archived webcast of the event or review the eventual transcript can access those materials on FDA’s website here.

This informal hearing was the beginning of an information-gathering phase for FDA, which will continue through January 9, 2017 – it is accepting written comments on the topic until that date and we recommend that all affected stakeholders submit their feedback to the Agency (Docket Number FDA-2016-N-1149). It remains to be seen what actions FDA will take in response to the increasing public pressure to reform its policies related to off-label communications.

Will FDA proceed in a stepwise fashion, as urged by some members of industry, to permit certain communications with payors first, then move on to more complicated and controversial circumstances? Will the Agency immediately issue a draft guidance to explain how it is going to integrate First Amendment concerns into its policies on manufacturer communications? While we don’t yet know which approach FDA will take, rest assured that we will be watching FDA’s next steps closely and will report back on any future developments in this area.

Joanne Hawana is Of Counsel in the firm and is based in our Washington, DC office. Her practice focuses on advising US and international clients in the food, drug, medical device and biotechnology industries on the business impacts of new US federal and state actions affecting regulated products. Joanne has in-depth knowledge of US federal drug regulations, including pre-market and post-market requirements as well as restrictions on advertising and sampling. She regularly works with clients to draft and submit public comments to agency rulemaking dockets, and frequently analyzes and summarizes new legislation and regulations with client interests in mind.

Benjamin Zegarelli is an Associate in the firm’s Health Law Practice. He provides counsel on compliance and regulatory issues to clients in the pharmaceutical, medical device, and biotech industries. With a clear focus on FDA regulatory counseling, Benjamin advises a breadth of health care industry clients on the federal and state laws surrounding manufacturer product development and marketing. His practice also includes advising clients on research approval, sales, and negotiating contractual relationships. Benjamin has given numerous presentations on current health care industry topics and held the position of Executive Editor of the Cardozo Law Review.

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